We have isolated a glycoprotein from normal human urine which produced hypertension when chronically administered in rats. The hypertension was associated with expanded plasma volume, retention of Na+ and increased aldosterone production. The compound has now been prepared in a pure form and has been named as Aldosterone Stimulating Factor (ASF). Our studies to date point towards the evidence that this a new hormone. ASF has been localized in the anterior lobe of the pituitary gland, has been detected in circulation, and the adrenal glands appear to be the target organ. Recently, we have identified a smaller fragment of ASF which is also biologically active. Our goals are to: a) define the mechanism of action for the aldosterone production and regulatory processes for its release; b) quantitation of ASF in blood, tissue and urine, to demonstrate its physiological significance; c) purify, quantitate and characterize the small ASF and define its physiological importance. In a preliminary study, ASF has been found to be significantly (5-fold) elevated in the urine of patients with confirmed adrenal hyperplasia and was not detectable in hypophysectomized patients' urine. This observation implied that ASF may be of considerable physiological significance in some diseased states (primary aldosteroidism). The present study is expected to demonstrate if ASF is indeed responsible for the etiology of some types of human hypertension. Once we know the mode of stimulation and mechanism of release of ASF, proper antagonists or drugs could be developed to prevent development of hypertension in these patients.